The goal of the study is to assess the interaction of heavy metals with the developing neural barrier transport systems. The objective will be achieved by studying (a) the uptake of the metals by barrier sites (choroid plexus, meninges and paraventricular tissue); (b) the effects of the metal on the barrier systems for translocation of neurally active solutes - calcium, hexoses and amino acids. To define patterns of barrier tissue distribution that correlate with neurotoxicity, we will study two neurotoxic metals, Pb(NO3)2 and a non-neurotoxic agent, Cd(Cl2). Flux across the combined neural barrier membranes will be measured by the single injection indicator dilution technique of Olendorf, modified to allow timed jugular venous sampling. A technique will also be developed to monitor discretely flow across the blood-CSF barrier, determined from arteriovenous transit of solutes across the isolated choroid plexus in vivo. All experiments will be performed in developing albino rabbits and the design will allow study of the effects of poisoning introduced at different developmental stages, and will contrast effects of acute high dose and chronic low level exposure. Isotope levels (203Pb, 203Hg, 109Cd, 45Ca, 14C-0-methyl-glucose and 14C-L-tryptophan) will be determined by liquid scintillation or gamma spectroscopy and metal levels will be determined by atomic absorption spectroscopy.